Advertisement

Comparing the effect of two different interfaces on breathing of preterm infants at birth: A matched-pairs analysis

Open AccessPublished:October 16, 2020DOI:https://doi.org/10.1016/j.resuscitation.2020.10.004

      Abstract

      Objective

      Applying a face mask could provoke a trigeminocardiac reflex. We compared the effect of applying bi-nasal prongs with a face mask on breathing and heart rate of preterm infants at birth.

      Methods

      In a retrospective matched-pairs study of infants <32 weeks of gestation, the use of bi-nasal prongs for respiratory support at birth was compared to the use of a face mask. Infants who were initially breathing at birth and subsequently received respiratory support were matched for gestational age (±4 days), birth weight (±300 g), general anaesthesia and gender. Breathing, heart rate and other parameters were collected before and after interface application and in the first 5 min thereafter.

      Results

      In total, 130 infants were included (n = 65 bi-nasal prongs, n = 65 face mask) with a median (IQR) gestational age of 27+2 (25+3–28+4) vs 26+6 (25+3–28+5) weeks. The proportion of infants who stopped breathing after applying the interface was not different between the groups (bi-nasal prongs 43/65 (66%) vs face mask 46/65 (71%), p = 0.70). Positive pressure ventilation was given more often when bi-nasal prongs were used (55/65 (85%) vs 40/65 (62%), p < 0.001). Heart rate (101 (75–145) vs 110 (68–149) bpm, p = 0.496) and oxygen saturation (59% (48–87) vs 56% (35–84), p = 0.178) were similar in the first 5 min after an interface was applied in the infants who stopped breathing.

      Conclusion

      Apnoea and bradycardia occurred often after applying either bi-nasal prongs or a face mask on the face for respiratory support in preterm infants at birth.

      Abbreviations:

      AOP (apnoea of prematurity), CPAP (continuous positive airway pressure), FiO2 (fraction of inspired oxygen), GA (gestational age), HR (heart rate), LUMC (Leiden University Medical Centre), PEEP (positive end-expiratory pressure), PIP (positive inspiratory pressure), PPV (positive pressure ventilation), SI (sustained inflation), SpO2 (oxygen saturation), TCR (trigeminocardiac reflex)

      Keywords

      Introduction

      The majority of preterm infants breathe at birth, but this is often insufficient and respiratory support is needed.
      • O’Donnel C.P.F.
      • Kamlin C.O.F.
      • Davis P.G.
      • Morley C.J.
      Crying and breathing by extremely preterm infants immediately after birth.
      A face mask is commonly used as an interface between the infant and a ventilation device during non-invasive respiratory support. However, previous studies
      • Dolfin T.
      • Duffty P.
      • Wilkes D.
      • England S.
      • Bryan H.
      Effects of a face mask and pneumotachograph on breathing in sleeping infants.
      • Fleming P.J.
      • Levine M.R.
      • Goncalves A.
      Changes in respiratory pattern resulting from the use of a facemask to record respiration in newborn infants.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      have shown that applying a face mask can affect breathing in newborns, causing a significant decrease in breathing rate and an increase in tidal volumes or apnoea. A mechanism causing this response could be the trigeminocardiac reflex (TCR), which is an oxygen preserving brainstem reflex, highly prominent in newborns and infants. Stimulation of any branch of the trigeminal nerve along its course can provoke the peripheral TCR and result in apnoea, a sudden decrease in heart rate (HR), changes in blood pressure and gastric hypermotility.
      • Meuwly C.
      • Golanov E.
      • Chowdhury T.
      • Erne P.
      • Schaller B.
      Trigeminal cardiac reflex: new thinking model about the definition based on a literature review.
      The peripheral TCR can be subdivided into the diving reflex, oculocardiac reflex and the maxillo-mandibular reflex (also referred to as the nasopharyngeal reflex) and can be activated through stimulation of thermic receptors, stretch receptors or nociceptive receptors.
      • Meuwly C.
      • Golanov E.
      • Chowdhury T.
      • Erne P.
      • Schaller B.
      Trigeminal cardiac reflex: new thinking model about the definition based on a literature review.
      • Buchholz B.
      • Kelly J.
      • Bernatene E.A.
      • Mendez Diodati N.
      • Gelpi R.J.
      Antagonistic and synergistic activation of cardiovascular vagal and sympathetic motor outflows in trigeminal reflexes.
      An airstream (temperature 25 °C) used for giving continuous positive airway pressure (CPAP) could stimulate the receptors of the trigeminal nerve in the nasal mucosa and the skin when given for 10 s.
      • Ramet J.
      • Praud J.-P.
      • D’Attest A.-M.
      • Dehan M.
      • Gaultier C.
      Trigeminal airstream stimulation.
      Pressing the mask on the face in order to acquire an adequate seal and prevent leak could also activate the stretch receptors in any of the three branches of the trigeminal nerve and provoke the TCR.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      • Buchholz B.
      • Kelly J.
      • Bernatene E.A.
      • Mendez Diodati N.
      • Gelpi R.J.
      Antagonistic and synergistic activation of cardiovascular vagal and sympathetic motor outflows in trigeminal reflexes.
      • Ramet J.
      • Praud J.-P.
      • D’Attest A.-M.
      • Dehan M.
      • Gaultier C.
      Trigeminal airstream stimulation.
      It is possible that the TCR has a stimulation threshold, as a reduction in breathing rate and an increase in tidal volume was not observed when a lightweight cardboard was applied in comparison to a face mask (rim).
      • Dolfin T.
      • Duffty P.
      • Wilkes D.
      • England S.
      • Bryan H.
      Effects of a face mask and pneumotachograph on breathing in sleeping infants.
      Therefore, avoiding the sensitive area around the mouth by using an alternative interface could possibly decrease the chance for inducing the TCR.
      We hypothesised that using bi-nasal prongs could reduce the effects of the TCR on breathing and HR in comparison to a face mask. The aim of this retrospective matched-pairs study was to compare the effect of applying bi-nasal prongs with a face mask on breathing and HR of preterm infants.

      Methods

      A retrospective matched-pairs study was performed in infants between 24+0 and 31+6 weeks of gestation. Infants were included from a database containing all recorded resuscitation videos of preterm infants (<32 weeks) receiving respiratory support via bi-nasal prongs or face mask from January 2012 until October 2018 at the General University Hospital in Prague and from March 2014 until October 2018 at Leiden University Medical Centre (LUMC).
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      Recordings were included if spontaneous breathing was present before the application of an interface. Infants were matched using IBM statistics SPSS version 25 (IBM Software, Chicago, Illinois, USA, 2016) on a 1:1 basis using gestational age (±4 days), birth weight (±300 g), general anaesthesia and gender as the comparators. Recordings were excluded if (1) it was impossible to determine the moment of interface application, (2) the type of interface was changed. A convenience sample was used based on the number of recordings in which bi-nasal prongs were used as respiratory support interface.
      In Leiden, respiratory support was provided by the Neopuff™ T-Piece resuscitator (Neopuff™ Infant Resuscitator, Fisher & Paykel Healthcare Ltd., Auckland, New Zealand) via face mask (Neonatal Resuscitation Mask, Fisher & Paykel Healthcare Ltd, Auckland, New Zealand). CPAP was initially given and in case of apnoea and/or bradycardia up to two sustained inflations (SI) for 15 s (PIP 20–25 cm H2O) and positive pressure ventilation (PPV; positive end-expiratory pressure (PEEP) of 5 cm H2O and peak inspiratory pressure (PIP) of 20–25 cm H2O) with a frequency of 40–60/min were given. The fraction of inspired oxygen (FiO2) was initially set at 0.3 and titrated based on the 25th percentile of the Dawson nomogram.
      • Dawson J.A.
      • Kamlin C.O.
      • Vento M.
      • et al.
      Defining the reference range for oxygen saturation for infants after birth.
      Physiological measurements were collected using a respiratory function monitor (Advanced Life Diagnostics, Weener, Germany) and the Polybench physiological software (Applied Biosignals, Weener, Germany), as described previously.
      • Dekker J.
      • Martherus T.
      • Cramer S.J.E.
      • van Zanten H.A.
      • Hooper S.B.
      • te Pas A.B.
      Tactile stimulation to stimulate spontaneous breathing during stabilization of preterm infants at birth: a retrospective analysis.
      In Prague, respiratory support was provided by Neopuff™ Infant T-piece Resuscitator (Neopuff™ Infant Resuscitator, Fisher & Paykel Healthcare Ltd., Auckland, New Zealand) via face mask (Laerdal Medical, Stavanger, Norway) or Argyle™ CPAP rubber bi-nasal cannula (Argyle CPAP Nasal Cannula, Covidien, Mansfield, MA, USA). The Argyle™ bi-nasal prongs became part of standard care, as it might avoid frequent complication associated with a face mask (e.g. leak, obstruction and provocation of trigeminal reflexes) and is compatible with the Neopuff. The short and rigid prongs allowed a quick and easy introduction without an increased risk of occlusion due to external pressure of the narrow aperture of the nose. As there was clinical equipoise regarding the two interfaces, the choice for which type of interface to use, was left to the discretion of the caregiver and was made before the infant's condition was evaluated. To minimise leak during nasal support, the nasal cannula leaf's were held in place manually by placing the thumb and the second finger on the upper jaw, while the mouth was closed by a lower jaw thrust using the remaining fingers of the same hand. CPAP was initially given and in case of apnoea and/or bradycardia up to three SI for 15–20 s (1st SI: 20 s, 2nd/3rd SI: 15 s, PIP 20–25 cm H2O) and PPV (PEEP of 5 cm H2O, PIP of 25 cm H2O) with a frequency of 40–60/min were given. The FiO2 was initially set at 0.3 and titrated based on the 25th percentile of the Dawson nomogram.
      • Dawson J.A.
      • Kamlin C.O.
      • Vento M.
      • et al.
      Defining the reference range for oxygen saturation for infants after birth.
      Physiological measurements were monitored using a Masimo pulse oximeter (Masimo Radical, Masimo Corporation, Irvine, California, USA) and software TRAL (SPM-Service, Zelenograd, Russia). All included infants received respiratory support after cord clamping or cord milking.
      Video recordings were reviewed, at normal and half speed, and documented in a case report form.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      All the recordings were reviewed by one researcher (KK) and in case of doubt consensus was reached with the help of a second researcher (TL/TM). Gestational age (GA), birth weight, gender, Apgar score at 1 and 5 min after birth, umbilical cord blood pH, mode of delivery, antenatal corticosteroids and the use of general anaesthetics were collected from the medical records of all included infants to describe baseline characteristics.
      The primary study outcome was the proportion of infants who were initially breathing at birth and stopped breathing after application of an interface. Initial breathing at birth was defined as chest excursions visible, crying and/or vivid spontaneous movements of the extremities in the time before the interface was applied. Breathing after applying an interface was defined as chest excursions visible 10–60 s after application of an interface or until the start of PPV, when given within 60 s. If infants only took breaths during sustained inflation, they were classified as stopped breathing, since no spontaneous breaths were observed without intervention.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      The other study outcomes included the use of SI, PPV, tactile stimulation, suctioning and intubation in the first 5 min after an interface was applied. In addition, HR, oxygen saturation (SpO2) and FiO2 were noted before and 10 s, 30 s, 1 min and 5 min after an interface was applied. SI was defined as a pressure-controlled inflation (20–25 cm H2O) sustained for at least 3 s.
      The local institutional Research Ethics Committee of the General University Hospital in Prague and the LUMC approved the study protocol and issued a statement of no objection for performing this study.

      Statistical analysis

      Categorical data are presented as n (%), continuous variables are presented as mean ± SD, for normally distributed values, or median (IQR) for non-normal data. Normality was judged from the inspection of histograms. To account for matching, paired tests or mixed effects models were used. The primary analysis was conducted using the related samples McNemar test. Other group comparisons were analysed using the McNemar test (dichotomous variables), the paired samples T-test (normally distributed continuous variables), or the related samples Wilcoxon Rank test (non-normally distributed values). The respective test is mentioned in the corresponding reporting table. A mixed model with a random intercept per individual and matched pair was used to analyse HR, SpO2 and FiO2 over the whole time period. Covariates in the mixed model were group (the variable of interest), time and an indicator variable for time including and beyond 600 s. The indicator variable was added to the model as there was a marked change at that time point for all measurements which was incompatible with a linear trend. To compare HR, SpO2 and FiO2 of the collected time points in the first 5 min after applying the interface measurements are reported per time point as median (IQR). Differences between groups over the whole first 5 min is evaluated using the group covariate of the mixed model (reported as mixed model P-value). Model details are included in a supplement. Mixed models were analysed with R, version 3.5.0 (Foundation for Statistical Computing, Vienna, Austria). All other analyses were conducted in SPSS. A p-value < 0.05 was considered statistically significant.

      Results

      There were 361 and 70 eligible recordings available with respiratory support via face mask and bi-nasal prongs, respectively. Using the matching criteria, we were able to match 65 infants supported via bi-nasal prongs with 65 infants supported via face mask. All infants in the bi-nasal prongs group were born in Prague, whereas 24/65 (37%) infants in the face mask group were born in Prague and 41/65 (63%) infants were born in Leiden. (Fig. 1) Baseline characteristics were not different between both groups. (Table 1)
      Fig. 1
      Fig. 1Study population. 65 infants who were initially breathing at birth and received respiratory support via bi-nasal prongs were matched for gestational age (±4 days), birth weight (±300 g), general anaesthesia and gender to 65 infants who were initially breathing at birth and received respiratory support via face mask. Of the infants receiving respiratory support via face mask, 41/65 (63%) infants were born at the LUMC and 24/66 (37%) at the General University Hospital in Prague.
      Table 1Characteristics of the patients.
      Patients’ characteristicsBi-nasal prongs

      N = 65
      Face mask

      N = 65
      p-Value
      Gestational age in weeks, median (IQR)27+2 (25+3–28+4)26+6 (25+3–28+5)
      Birth weight in grams, mean ± SD927 ± 288946 ± 268
      General anaesthesia, n (%)19 (29)19 (29)
      Male, n (%)39 (60)39 (60)
      Complete course of antenatal corticosteroids, n (%)41 (63)28 (43)0.067
      Related-samples McNemar test.
      Caesarean delivery, n (%)41 (63)38 (59)0.664
      Related-samples McNemar test.
      Apgar score 1 min, mean ± SD5 ± 25 ± 20.324
      Paired-samples T-test.
      Apgar score 5 min, mean ± SD8 ± 17 ± 20.342
      Paired-samples T-test.
      Umbilical cord blood pH, median (IQR)7.34 (7.26–7.39)7.33 (7.54–7.39)0.861
      Related-samples Wilcoxon signed rank test.
      a Related-samples McNemar test.
      b Paired-samples T-test.
      c Related-samples Wilcoxon signed rank test.
      The proportions of infants who stopped breathing after the interface was applied were not different between the groups (bi-nasal prongs: 43/65 (66%) vs face mask: 46/65 (71%) infants, p = 0.700). SI tended to be given more often (44/65 (68%) vs 33/65 (51%) infants, p < 0.01) and PPV was given more often (55/65 (85%) vs 40/65 (62%) infants, p < 0.001) in the bi-nasal prongs group, without a difference in starting time of PPV after the start of respiratory support (49 (26–82) vs 60 (24–98) seconds, p = 0.446). Tactile stimulation was performed frequently in both groups, while suction was performed more often in the bi-nasal prongs group (53/65 (82%) vs 23/65 (35%) infants, p < 0.001) and was also repeated more often (second time: 23/65 (35%) vs 5/65 (8%) infants, p < 0.001, third time: 6/65 (9%) vs 2/65 (3%) infants, p = 0.289). (Table 2)
      Table 2Delivery room outcomes.
      OutcomeBi-nasal prongs

      N = 65
      Face mask

      N = 65
      p-Value
      Thorax excursions
      After application of an interface.
      , n (%)
      0.700
      Related-samples McNemar test.
       Visible (continued breathing)22 (34)19 (29)
       Not visible (stopped breathing
      Stopped breathing includes also infants with only visible thorax excursions during SI.
      )
      43 (66)46 (71)
      PPV is given, n (%)55 (85)40 (62)0.001
      Related-samples McNemar test.
      Time until start PPV
      After application of an interface.
      (s), median (IQR)
      49 (26–82)60 (24–98)0.446
      Related-samples Wilcoxon signed rank test.
      SI is given, n (%)44 (68)33 (51)0.082
      Related-samples McNemar test.
      Only thorax excursions during SI, n (%)11 (25)13 (39)0.508
      Related-samples McNemar test.
      Based on N = 22 matched pairs in which both infants received SI.
      Tactile stimulation, n (%)59 (91)57 (88)0.774
      Related-samples McNemar test.
      Suction, n (%)53 (82)23 (35)<0.001
      Related-samples McNemar test.
      Time until suctioning was performed
      After application of an interface.
      (s), median (IQR)
      38 (9–62)59 (-7-149)0.469
      Related-samples Wilcoxon signed rank test.
      Intubation rate, n (%)6 (9)7 (11)1.000
      Related-samples McNemar test.
      PPV – positive pressure ventilation; SI – sustained inflation.
      a After application of an interface.
      b Stopped breathing includes also infants with only visible thorax excursions during SI.
      c Related-samples McNemar test.
      d Related-samples Wilcoxon signed rank test.
      e Based on N = 22 matched pairs in which both infants received SI.
      There was no statistically significant difference in HR and SpO2 in the first 5 min of the infants who stopped breathing after application of an interface (HR 101 (71–145) vs 110 (68–149) bpm, p = 0.496 (mixed model); SpO2 59% (48–87) vs 56% (35–84), p = 0.178 (mixed model)), but less FiO2 was given in the bi-nasal prongs group at 5 min (0.30 (0.21–0.50) vs 0.56 (0.34–0.98), p < 0.01 (mixed model)) (Fig. 2, Supplementary Table 1).
      Fig. 2
      Fig. 2Data of infants who stopped breathing after interface application, is presented as median (IQR). Time = 0 represent the measurement before interface application. (A) Heart rate. Data of infants who received respiratory support via bi-nasal prongs or face mask was calculated based on n = 4 and n = 1 at t = 0, respectively, and n = 10 and n = 6 at t = 10. All other presented data is based on n ≥ 20. (B) Oxygen saturation. Data of infants who received respiratory support via bi-nasal prongs or face mask is calculated based on n = 4 and n = 1 at t = 0, respectively, and n = 9 and n = 8 at t = 10. All other presented data is based on n ≥ 19.

      Discussion

      In this retrospective matched-pairs study we observed that the occurrence of apnoea was high and similar in both groups after applying either the bi-nasal prongs or face mask. This finding suggests that both interfaces, bi-nasal prongs and face mask, are associated with apnoea and/or bradycardia and have the potential of triggering the TCR and thereby increasing the need for PPV. However, to demonstrate whether or not there is a causative relationship mediated through TCR a prospective design would be needed. Nonetheless, we expect the apnoea to be caused by the interface as the apnoea was typically seen right after applying the interface and a previous study showed that infants stopped breathing after a median time of 5 s after applying a face mask.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      This is the first study to compare the effect of two interfaces on breathing in preterm infants at birth. We hypothesised that using a different interface which avoided stimulating the sensitive area around the nose and mouth could decrease the effects of the TCR, but were unable to confirm this. The mechanism of the TCR is still relatively unknown in preterm infants and the reason for inducing TCR while using nasal prongs is unclear. Apparently, the threshold to provoke the TCR was still reached or a different pathway was stimulated when nasal prongs were used. It is possible that the bi-nasal prongs provided a sufficient stimulus to the trigeminal nerve by activating the trigeminal receptors inside the nose or the receptors associated with holding the leafs of the bi-nasal prongs to the upper jaw and closing the mouth.
      The use of a face mask with a single nasal tube for stabilisation of preterm infants at birth has been previously compared in a randomised controlled clinical trial.
      • van Vonderen J.J.
      • Kamlin C.O.
      • Dawson J.A.
      • Walther F.J.
      • Davis P.G.
      • te Pas A.B.
      Mask versus nasal tube for stabilization of preterm infants at birth: respiratory function measurements.
      Although, breathing before and after interface application was not investigated, no difference in breathing rate was observed in the first 5 min after the start of respiratory support as well as no differences in SpO2 and HR.
      • van Vonderen J.J.
      • Kamlin C.O.
      • Dawson J.A.
      • Walther F.J.
      • Davis P.G.
      • te Pas A.B.
      Mask versus nasal tube for stabilization of preterm infants at birth: respiratory function measurements.
      Holding the single nasal tube and closing the mouth and other nostril could have caused a similar effect in studies using a single nasal tube
      • van Vonderen J.J.
      • Kamlin C.O.
      • Dawson J.A.
      • Walther F.J.
      • Davis P.G.
      • te Pas A.B.
      Mask versus nasal tube for stabilization of preterm infants at birth: respiratory function measurements.
      • Kamlin C.O.F.
      • Schilleman K.
      • Dawson J.A.
      • et al.
      Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial.
      • McCarthy L.K.
      • Twomey A.R.
      • Molloy E.J.
      • Murphy J.F.A.
      • O’Donnell C.P.F.
      A Randomized trial of nasal prong or face mask for respiratory support for preterm newborns.
      as described in our current study. Nonetheless, trigeminal stimulation and thereby provocation of the TCR might still be reduced when the mouth is gently closed with only one finger and alternative bi-nasal prongs without leaf's and the need for fixation are used.
      In this study, more infants stopped breathing after face mask application when compared to our previous study (71% vs 54%).
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      This is likely the result of the differences in median GA as infants with a lower GA were included in our current study and we previously demonstrated that the occurrence of apnoea is inversely associated with gestation.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      PPV was more often given when bi-nasal prongs were used. This result is consistent with the results of McCarthy et al.
      • McCarthy L.K.
      • Twomey A.R.
      • Molloy E.J.
      • Murphy J.F.A.
      • O’Donnell C.P.F.
      A Randomized trial of nasal prong or face mask for respiratory support for preterm newborns.
      who compared a single nasal tube with face mask. However, Kamlin et al.
      • Kamlin C.O.F.
      • Schilleman K.
      • Dawson J.A.
      • et al.
      Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial.
      observed no difference in PPV in the delivery room when comparing a single nasal tube and a face mask. Although the main cause of these divergent findings is unclear, the decision to start PPV likely varies between caregivers and centres. In this study, all infants in the bi-nasal prongs group were born in Prague, while the majority of infants in the face mask group were born in Leiden. We speculate that the use of respiratory function monitor, which is standard care in Leiden, likely influenced this difference, since it is difficult to identify spontaneous breathing in preterm infants, whereas use of a monitor increases the likelihood of detecting breaths.
      • Poulton D.A.
      • Schmolzer G.M.
      • Morley C.J.
      • Davis P.G.
      Assessment of chest rise during mask ventilation of preterm infants in the delivery room.
      To explore the impact of the different centres we compared all infants born in Prague and the occurrence of PPV was not significantly different between groups (bi-nasal prongs vs face mask; 86% (60/70) vs 72% (42/58), p = 0.063). This suggest that the difference in occurrence of PPV might be due to a lower tendency to use PPV in Leiden. It is also noteworthy that some infants stopped breathing after interface placement and started breathing again after SI's, making PPV unnecessary. This explains the discrepancy between the number of infants that stopped breathing after applying a face mask (71%) and the number of infants receiving PPV (62%).
      In this study, suctioning was more frequently performed in the bi-nasal prongs group. These results need to be interpreted with the appropriate caution, since this finding might be the result of differences in practice between centres. However, there is a lower threshold for suctioning with bi-nasal prongs, because the respiratory support does not have to be interrupted, in contrast to when a face mask is used.
      • Capasso L.
      • Capasso A.
      • Raimondi F.
      • Vendemmia M.
      • Araimo G.
      • Paludetto R.
      A randomized trial comparing oxygen delivery on intermittent positive pressure with nasal cannulae versus facial mask in neonatal primary resuscitation.
      Although suctioning can lead to vagal-induced bradycardia or apnoea, it is unlikely that this influenced our findings, as we only counted apnoea's that occurred directly after placement of the interface in infants who were breathing and suctioning was usually performed just before the start of PPV or during PPV. However, it is possible that the more frequent use of suctioning could have led to an increased need for PPV in the bi-nasal prongs group as some infants continued breathing after placing the interface, but stopped breathing after suctioning for which then PPV was given.
      It is known that applying a face mask (rim) and/or airflow affect breathing in newborns.
      • Dolfin T.
      • Duffty P.
      • Wilkes D.
      • England S.
      • Bryan H.
      Effects of a face mask and pneumotachograph on breathing in sleeping infants.
      • Fleming P.J.
      • Levine M.R.
      • Goncalves A.
      Changes in respiratory pattern resulting from the use of a facemask to record respiration in newborn infants.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      • Ramet J.
      • Praud J.-P.
      • D’Attest A.-M.
      • Dehan M.
      • Gaultier C.
      Trigeminal airstream stimulation.
      CPAP is commonly used as treatment for apnoea of prematurity (AOP).
      • Zhao J.
      • Gonzalez F.
      • Mu D.
      Apnea of prematurity: from cause to treatment.
      This suggests that when CPAP is continuously given directly into the nostrils the cutaneous receptors and the receptors in the nasal cavity of the trigeminal nerve do not reach the threshold for provoking the TCR or the receptors adapt rapidly and the response diminishes with time. Since the primary factor to trigger the TCR is a decrease in intranasal temperature
      • Tsubone H.
      Nasal ‘flow’ receptors of the rat.
      and CPAP is commonly continuously administered with an air temperature of 37 °C it can be safely used as treatment for AOP. Experimental studies are needed to investigate whether or not starting CPAP could provoke the TCR independently of the interface and if gradually increasing flow or PEEP at the start of CPAP might avoid triggering it.
      This was a retrospective matched-pairs study and the results should be interpreted with the appropriate caution. The decision for which interface to use and to start SI, PPV, tactile stimulation, suction and intubation depended on the local protocols and discretion of the caregivers. This also includes the small differences in resuscitation algorithms between the two centres, which might have influenced our results. Analyses of the recordings were dependent on the visibility of the infant's chest and only a small proportion of physiological measurements were available. The infants of whose physiological measurements were available were more likely stable infants as they are more likely to receive respiratory support after the pulse oximetry probe is applied. They also have a better peripheral perfusion, increasing the chance to obtain adequate measurement before the interface is applied. This could have biased our observations and led to an underestimation of the effects on SpO2 and HR.
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      Recordings were reviewed by only one researcher, however, our previous study
      • Kuypers K.L.A.M.
      • Lamberska T.
      • Martherus T.
      • et al.
      The effect of a face mask for respiratory support on breathing in preterm infants at birth.
      did show that the majority of the observations on the video could be verified with RFM recordings, which can be considered golden standard. Therefore, we expect the inaccuracy to be minimal. In addition, we used a convenience sample based on availability of recordings where bi-nasal prongs were used to effectuate matching.

      Conclusion

      In conclusion, there were no differences observed in breathing and heartrate after application of the bi-nasal prongs in comparison to a face mask. Clinicians should be aware that applying an interface could compromise breathing in preterm infants at birth. It is possible that applying an interface stimulates the trigeminal nerve and provoke the TCR as long as the sensitive area around mouth and nose is stimulated. Further studies are warranted to investigate the mechanism of the TCR before an interface can be recommended or developed to minimise the chance for a TCR.

      Conflict of interest

      None.

      Funding

      None of the authors has financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. Prof. Dr. A.B. te Pas is recipient of a NWO innovational research incentives scheme (VIDI 91716428).

      Authors’ contribution

      KK, TL, TM, AP designed the study; KK, TL acquired the data; KK, TM, SB analysed the data; KK, TL, TM, JD, SH, RP and AP were involved with the data interpretation. All authors contributed to the final draft by reviewing the manuscript. No honorarium, grant or other form of payment was given to anyone to produce the manuscript.

      Appendix A. Supplementary data

      The following are the supplementary data to this article:

      References

        • O’Donnel C.P.F.
        • Kamlin C.O.F.
        • Davis P.G.
        • Morley C.J.
        Crying and breathing by extremely preterm infants immediately after birth.
        J Pediatr. 2010; 156: 846-847
        • Dolfin T.
        • Duffty P.
        • Wilkes D.
        • England S.
        • Bryan H.
        Effects of a face mask and pneumotachograph on breathing in sleeping infants.
        Am Rev Respir Dis. 1983; 128: 977-979
        • Fleming P.J.
        • Levine M.R.
        • Goncalves A.
        Changes in respiratory pattern resulting from the use of a facemask to record respiration in newborn infants.
        Pediatr Res. 1982; 16: 1031-1034
        • Kuypers K.L.A.M.
        • Lamberska T.
        • Martherus T.
        • et al.
        The effect of a face mask for respiratory support on breathing in preterm infants at birth.
        Resuscitation. 2019; 144: 178-184
        • Meuwly C.
        • Golanov E.
        • Chowdhury T.
        • Erne P.
        • Schaller B.
        Trigeminal cardiac reflex: new thinking model about the definition based on a literature review.
        Medicine (Baltimore). 2015; 94: e484
        • Buchholz B.
        • Kelly J.
        • Bernatene E.A.
        • Mendez Diodati N.
        • Gelpi R.J.
        Antagonistic and synergistic activation of cardiovascular vagal and sympathetic motor outflows in trigeminal reflexes.
        Front Neurol. 2017; 8: 52
        • Ramet J.
        • Praud J.-P.
        • D’Attest A.-M.
        • Dehan M.
        • Gaultier C.
        Trigeminal airstream stimulation.
        Chest. 1990; 98: 92-96
        • Dawson J.A.
        • Kamlin C.O.
        • Vento M.
        • et al.
        Defining the reference range for oxygen saturation for infants after birth.
        Pediatrics. 2010; 125: e1340-e1347
        • Dekker J.
        • Martherus T.
        • Cramer S.J.E.
        • van Zanten H.A.
        • Hooper S.B.
        • te Pas A.B.
        Tactile stimulation to stimulate spontaneous breathing during stabilization of preterm infants at birth: a retrospective analysis.
        Front Pediatr. 2017; : 5
        • van Vonderen J.J.
        • Kamlin C.O.
        • Dawson J.A.
        • Walther F.J.
        • Davis P.G.
        • te Pas A.B.
        Mask versus nasal tube for stabilization of preterm infants at birth: respiratory function measurements.
        J Pediatr. 2015; 167 (81-5e1)
        • Kamlin C.O.F.
        • Schilleman K.
        • Dawson J.A.
        • et al.
        Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial.
        Pediatrics. 2013; 132: e381-e388
        • McCarthy L.K.
        • Twomey A.R.
        • Molloy E.J.
        • Murphy J.F.A.
        • O’Donnell C.P.F.
        A Randomized trial of nasal prong or face mask for respiratory support for preterm newborns.
        Pediatrics. 2013; 132: e389-e395
        • Poulton D.A.
        • Schmolzer G.M.
        • Morley C.J.
        • Davis P.G.
        Assessment of chest rise during mask ventilation of preterm infants in the delivery room.
        Resuscitation. 2011; 82: 175-179
        • Capasso L.
        • Capasso A.
        • Raimondi F.
        • Vendemmia M.
        • Araimo G.
        • Paludetto R.
        A randomized trial comparing oxygen delivery on intermittent positive pressure with nasal cannulae versus facial mask in neonatal primary resuscitation.
        Acta Paediatr. 2005; 94: 197-200
        • Zhao J.
        • Gonzalez F.
        • Mu D.
        Apnea of prematurity: from cause to treatment.
        Eur J Pediatr. 2011; 170: 1097-1105
        • Tsubone H.
        Nasal ‘flow’ receptors of the rat.
        Respir Physiol. 1989; 75: 51-64